In-silico ANALYSIS OF (S)-PINOSTROBINBENZOATE DERIVATIVES FROM Boesenbergia pandurata Roxb. AS THE CYCLOOXYGENASE-2 INHIBITORS IN FINDING ANTI-INFLAMMATORY DRUG CANDIDATES

Abstract

Boesenbergia pandurata Roxb. Schlecht, often known as Temu kunci, contains the flavonoid pinostrobin in its rhizome. It is useful against inflammation because it can suppress the cyclooxygenase-2 (COX-2) enzyme. The goal of this work is to develop (S)-pinostrobinbenzoate derivatives, a chemical that inhibits inflammation on COX-2 targets, to use in silico analysis to find possible candidates for anti-inflammatory drugs. In this work, 20 compounds of (S)- pinostrobinbenzoate derivatives were the subject of an in silico investigation using PASS online to predict the substance activity spectrum (PASS) and MOE 2022.02 for molecular docking on the COX-2 enzyme (PDB code 1CX2). The pkCSM Online application was also used to estimate ADMET characteristics. The structure-activity relationships of the selected compounds were examined by the quantitative structure-property relationships (QSPR) approach. The results showed that (S)-pinostrobin 2-methoxybenzoate had a strong affinity for COX-2 based on molecular docking, as indicated by a free binding energy (S value) of -9.16 kcal/mol. From PASS online it was found that a COX-2 inhibitor, has an "active" probability (Pa) of 0.763, giving it a viable option for anti-inflammatory medications. Based on ADMET prediction, (S)-pinostrobinbenzoate derivatives displayed high specificity and sufficient BBB permeability. The QSPR analysis indicated that the lipophilic character (logP) of the (S)- pinostrobinbenzoate derivatives relates to its in-silico activity against COX-2. This work provided a solid basis for subsequent investigations to combine and assess the anti-inflammatory effects in vitro and in vivo, then the pre-clinic and clinical trial pertaining to the development of the (S)-pinostrobinbenzoate.